Immunotherapy Group Research Articles

Anti-GD2 Based Immunotherapy Prevents Late Events in High-Risk Neuroblastoma Patients over 18 Months at Diagnosis.

Simple SummaryHigh-risk neuroblastoma accounts for 4% of newly diagnosed pediatric malignancies, but for 9–10% of pediatric cancer mortality. To reduce the number of (late) recurrences and subsequently improve survival, anti-GD2 monoclonal antibody based immunotherapy has been added to the maintenance phase of treatment. The first randomized study (ANBL0032) was ground breaking, showing a 20% improved event free survival. Subsequently immunotherapy was included in all international high-risk treatment regimens. Randomization will never be repeated. In this article we present additional data from our retrospective cohort to corroborate the ANBL0032 study. Our cohort contains 84 Dutch high-risk neuroblastoma patients. They were treated with GPOH or POG induction, followed by immunotherapy according to original ANBL0032 protocol (immunotherapy group) or single-agent isotretinoin (historical control group). In the complete cohort, 5 year OS was 64 ± 7% and 49 ± 8% for the immunotherapy group and the control group, respectively (p = 0.16). Five year EFS was 57 ± 7% and 41 ± 8%, respectively (p = 0.16). In the subgroup of patients ≥ 18 months, 5-yr OS was 63 ± 8% and 39 ± 9, respectively (p = 0.04) and EFS 54 ± 8% and 29 ± 8%, respectively (p = 0.05). Our five year data suggest a role for the immunotherapy in preventing late events, especially in patients ≥ 18 months old.Background: Anti-GD2 based immunotherapy has improved overall (OS) and event free survival (EFS) for high-risk neuroblastoma (HR-NBL) patients. Here, we evaluate the long-term efficacy of anti-GD2 immunotherapy in combination with isotretinoin, GM-CSF, and IL-2. Methods: Dutch HR-NBL patients treated with immunotherapy according to the COG-ANBL0032 protocol (n = 47) were included and compared to historical controls (n = 37) treated with single-agent isotretinoin maintenance therapy. Survival time was calculated from start of the maintenance therapy. Results: The study and control group were similar concerning baseline characteristics. In the complete cohort, 5 year OS was 64 ± 7% and 49 ± 8% for the immunotherapy group and the control group, respectively (p = 0.16). Five year EFS was 57 ± 7% and 41 ± 8%, respectively (p = 0.16). In the subgroup of patients ≥ 18 months, 5-yr OS was 63 ± 8% and 39 ± 9, respectively (p = 0.04) and EFS 54 ± 8% and 29 ± 8%, respectively (p = 0.05). Landmark analysis for EFS with landmark point at 6 months after start of maintenance suggests a larger effect on the prevention of late than early events. Conclusions: This study is the first to confirm the results of the COG-ANBL0032 study in a cohort treated with a different induction regimen. Anti-GD2 immunotherapy prevents late events, most significantly in patients older than 18 months of age at diagnosis.

PD40-10 COMPARATIVE EFFECTIVENESS OF FIRST-LINE IMMUNOTHERAPY, TARGETED THERAPY, AND COMBINATION THERAPY FOR METASTATIC CLEAR CELL RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) II (PD40)1 Sep 2021PD40-10 COMPARATIVE EFFECTIVENESS OF FIRST-LINE IMMUNOTHERAPY, TARGETED THERAPY, AND COMBINATION THERAPY FOR METASTATIC CLEAR CELL RENAL CELL CARCINOMA Nicholas Chakiryan, David Jiang, Kyle Gillis, Elizabeth Green, Ali Hajiran, Lee Hugar, Logan Zemp, Jad Chahoud, Jingsong Zhang, Rohit Jain, Wade Sexton, Scott Gilbert, and Brandon Manley Nicholas ChakiryanNicholas Chakiryan More articles by this author , David JiangDavid Jiang More articles by this author , Kyle GillisKyle Gillis More articles by this author , Elizabeth GreenElizabeth Green More articles by this author , Ali HajiranAli Hajiran More articles by this author , Lee HugarLee Hugar More articles by this author , Logan ZempLogan Zemp More articles by this author , Jad ChahoudJad Chahoud More articles by this author , Jingsong ZhangJingsong Zhang More articles by this author , Rohit JainRohit Jain More articles by this author , Wade SextonWade Sexton More articles by this author , Scott GilbertScott Gilbert More articles by this author , and Brandon ManleyBrandon Manley More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002050.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: As compared to targeted therapy (TT), clinical trials have shown an overall survival (OS) benefit for first-line immunotherapy (IT) and combination TT/IT regimens in metastatic clear cell renal cell carcinoma (RCC). Generalizability of these findings in a real-world cohort, outside of a clinical trial setting, is unclear. The primary objective is to assess the effect of first-line TT, IT, and combination TT/IT regimens on OS in a real-world cohort of patients with metastatic clear cell RCC. METHODS: This retrospective propensity-matched study identified patients with metastatic clear cell RCC in the National Cancer Database from 2015-2017 who received either first-line TT, IT, or combination TT/IT and were not treated on a clinical trial protocol. Patients were stratified by first-line systemic treatment. After 1:1:1 nearest-neighbor caliper-matching of propensity scores, survival analyses were conducted using Cox regression and Kaplan-Meier estimates. The primary outcome was OS from the date of diagnosis to death or censoring at last follow-up. RESULTS: The final study population included 5872 patients and the matched cohort included 1437 patients (479 per treatment group). Use of either IT or combination TT/IT increased over the time period studied (14.6%, 17.5%, and 24.3% in 2015, 2016, and 2017, respectively). Patients who were treated with either first-line IT or combination TT/IT had improved OS compared to those who were treated with first-line TT (IT group: HR 0.6 [95% CI, 0.48-0.75], p<.001; combination TT/IT group: HR 0.7 [95% CI, 0.60-0.91], p=.005). No survival difference was seen between the IT and combination TT/IT groups (combination TT/IT: HR 1.24 [95% CI, 0.98-1.56], p=.075). CONCLUSIONS: Patients with metastatic clear cell RCC who received first-line IT or combination TT/IT had improved OS compared to those who received first-line TT. These findings are similar to those identified in recently reported clinical trials, lending confidence to the broader applicability of these findings outside of a clinical trial setting. Source of Funding: NA © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e678-e678 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nicholas Chakiryan More articles by this author David Jiang More articles by this author Kyle Gillis More articles by this author Elizabeth Green More articles by this author Ali Hajiran More articles by this author Lee Hugar More articles by this author Logan Zemp More articles by this author Jad Chahoud More articles by this author Jingsong Zhang More articles by this author Rohit Jain More articles by this author Wade Sexton More articles by this author Scott Gilbert More articles by this author Brandon Manley More articles by this author Expand All Advertisement Loading ...

Prognostic value of blood cell count-derived ratios in BRAF-mutated metastatic melanoma.

The treatment and prognosis of metastatic melanoma have changed during the last decade to include immunotherapy or targeted therapy as standard therapeutic options for BRAF-mutated melanoma. However, predictive and/or prognostic markers are lacking, especially in clinical situations where several options are available. The aim of this study was to determine the association of pre-therapeutic blood cell count-derived ratios (BCDR) with survival in patients with BRAF-mutated metastatic melanoma. We evaluated the prognostic role of BCDR in therapy-naïve patients with BRAF-mutated metastatic melanoma treated with immune checkpoint inhibitors or targeted therapy. The impact of BCDR on survival was analysed using univariate and multivariate Cox proportional hazard models. We enrolled 46 patients treated with BRAF inhibitors and 20 patients who received anti-PD-1 checkpoint inhibitors. The median progression-free survival (PFS) and overall survival (OS) were 8.3 and 18.2 months, respectively, with no statistical difference between groups. The objective response rate was 39% (30% in the anti-PD-1 and 44% in the targeted therapy groups). Baseline BCDR values were associated with improved PFS and OS in the immunotherapy group. Only the platelet-to-lymphocyte ratio (PLR) was associated with OS and PFS in the targeted therapy group. Independent prognostic indicators for PFS were lactate dehydrogenase, PLR and the lymphocyte-to-monocyte ratio (LMR) and those for OS were LMR, toxicity and the number of initial metastases. BCDR had a substantial prognostic value in patients with BRAF-mutated metastatic melanoma treated with immune checkpoint inhibitors. However, a prognostic role for BCDR seemed less apparent in patients treated with targeted therapies.

Preliminary Report on Computed Tomography Radiomics Features as Biomarkers to Immunotherapy Selection in Lung Adenocarcinoma Patients.

Simple SummaryThe objective of the study was to assess the radiomics features obtained by computed tomography (CT) examination as biomarkers in order to select patients with lung adenocarcinoma who would benefit from immunotherapy. We demonstrated that specific radiomic features could be used to select patients with lung adenocarcinoma who would benefit from immunotherapy by predicting OS or PFS time.Purpose: To assess the efficacy of radiomics features obtained by computed tomography (CT) examination as biomarkers in order to select patients with lung adenocarcinoma who would benefit from immunotherapy. Methods: Seventy-four patients (median age 63 years, range 42–86 years) with histologically confirmed lung cancer who underwent immunotherapy as first- or second-line therapy and who had baseline CT studies were enrolled in this approved retrospective study. As a control group, we selected 50 patients (median age 66 years, range 36–86 years) from 2005 to 2013 with histologically confirmed lung adenocarcinoma who underwent chemotherapy alone or in combination with targeted therapy. A total of 573 radiomic metrics were extracted: 14 features based on Hounsfield unit values specific for lung CT images; 66 first-order profile features based on intensity values; 43 second-order profile features based on lesion shape; 393 third-order profile features; and 57 features with higher-order profiles. Univariate and multivariate statistical analysis with pattern recognition approaches and the least absolute shrinkage and selection operator (LASSO) method were used to assess the capability of extracted radiomics features to predict overall survival (OS) and progression free survival (PFS) time. Results: A total of 38 patients (median age 61; range 41–78 years) with confirmed lung adenocarcinoma and subjected to immunotherapy satisfied inclusion criteria, and 50 patients in a control group were included in the analysis The shift in the center of mass of the lesion due to image intensity was significant both to predict OS in patients subjected to immunotherapy and to predict PFS in patients subjected to immunotherapy and in patients in the control group. With univariate analysis, low diagnostic accuracy was reached to stratify patients based on OS and PFS time. Regarding multivariate analysis, considering the robust (two morphological features, three textural features and three higher-order statistical metrics) application of the LASSO approach and all patients, a support vector machine reached the best results for stratifying patients based on OS (area under curve (AUC) of 0.89 and accuracy of 81.6%). Alternatively, considering the robust predictors (six textural features and one higher-order statistical metric) and application of the LASSO approach including all patients, a decision tree reached the best results for stratifying patients based on PFS time (AUC of 0.96 and accuracy of 94.7%). Conclusions: Specific radiomic features could be used to select patients with lung adenocarcinoma who would benefit from immunotherapy because a subset of imaging radiomic features useful to predict OS or PFS time were different between the control group and the immunotherapy group.

Real-World Efficacy and Safety of Anlotinib With and Without Immunotherapy in Advanced Non-Small Cell Lung Cancer

AimsCombination of anti-angiogenesis therapy and immunotherapy has showed synergistic effects in non-small cell lung cancer (NSCLC). The aim of this retrospective study was to investigate the efficacy and safety of anlotinib with and without immunotherapy in NSCLC.MethodsPathologically confirmed NSCLC patients (stage IIIB-IV) receiving anlotinib between November 2018 and February 2020 were enrolled for retrospective analysis. The outcomes and safety of overall patients were evaluated, and the efficacies of anlotinib plus immunotherapy and anlotinib alone was compared. The primary endpoint was progression-free survival (PFS).ResultsA total of 80 patients (median age: 62 years, range: 29-86 years) were included. Overall median PFS was 4.3 months (95% confidence interval (CI): 2.7-5.9 months). In univariate analysis, patients without EGFR mutation, previous EGFR target therapy, and brain metastasis had significantly longer PFS. Cox regression analysis showed that only brain metastasis was an independent predictor of PFS. The median PFS of patients receiving anlotinib plus immunotherapy was slightly longer than that of patients receiving anlotinib alone (4.2 vs 3.1 months); however, the difference was not statistically significant. A tendency of longer median PFS was observed in patients with adenocarcinoma, EGFR wild type, stage IV, no liver metastasis, former smoker, ≥2 previous treatment lines, no previous VEGF or EGFR target therapies in anlotinib plus immunotherapy group. Treatments with anlotinib alone or anlotinib plus immunotherapy were well tolerable. The most common adverse events were fatigue, decreased hemoglobin count, hypertension, hand-foot syndrome, oral mucositis and hoarseness.ConclusionAnlotinib is well tolerable and effective in advanced NSCLC patients. Brain metastasis is an independent predictor of PFS in NSCLC patients receiving anlotinib. Future prospective studies with larger sample size and extended follow-up are needed to confirm the clinical benefit in NSCLC patients treated with anlotinib combined with immunotherapy.

Perioperative Outcomes and Survival After Preoperative Immunotherapy for Non-Small Cell Lung Cancer

BackgroundAlthough preoperative immunotherapy is increasingly utilized for non-small cell lung cancer, there remains a paucity of robust clinical data on its safety and long-term survival. Our objective was to evaluate the perioperative outcomes and survival associated with immunotherapy followed by surgery for patients with non-small cell lung cancer. MethodsOutcomes of patients with non-small cell lung cancer who underwent lung resection after preoperative chemotherapy with or without radiation or immunotherapy (with or without chemotherapy or chemoradiation) in the National Cancer Database (2010 to 2017) were evaluated using Kaplan-Meier analysis, multivariable logistic regression, multivariable Cox proportional hazards analysis, and propensity score-matched analysis. ResultsFrom 2010 to 2017, 236 patients (2.2%) received immunotherapy and 10 715 patients received preoperative chemotherapy followed by surgery. There were no significant differences between the immunotherapy and preoperative chemotherapy groups with regard to margin positivity (8.5% [n = 20] vs 7.5% [n = 715], P = .98), 30-day readmission (4.2% [n = 10] vs 4.1% [n = 440], P = .87), and 30-day mortality (0.4% [n = 1] vs 2.4% [n = 253], P = .25). The immunotherapy and preoperative chemotherapy groups had similar overall survival (5-year survival 63% [95% confidence interval, 50% to 74%] vs 51% [95% confidence interval, 50% to 52%], log rank P = .06; multivariable adjusted hazard ratio 0.98; 95% confidence interval, 0.67 to 1.41; P = .90). A propensity score matched analysis of 344 patients, well matched by preoperative characteristics, showed no significant differences in short-term outcomes and overall survival (log rank P = 1.00) between the two groups. ConclusionsIn this national analysis, preoperative immunotherapy followed by surgery for non-small cell lung cancer was found to be safe and feasible with similar short-term outcomes and overall survival when compared with preoperative chemotherapy followed by surgery.

Outcomes of Stereotactic Radiosurgery and Immunotherapy in Renal Cell Carcinoma Patients With Brain Metastases.

The impact of immunotherapy and stereotactic radiosurgery (SRS) in treatment of brain metastases (BM) from renal cell carcinoma (RCC) has not been well investigated. Forty-eight patients with 372 RCC BM were treated with SRS and divided into those ever treated with immunotherapy versus those who never received immunotherapy. Survival and local control (LC) outcomes were studied. χ2 and Mann-Whitney U tests compared categorical and continuous variables, respectively. Kaplan-Meier curves were used to estimate survival and log-rank test was used to compare survival between groups. Immunotherapy and nonimmunotherapy groups contained 29 and 19 patients, respectively. Median follow-up was 23.1 months (range, 6 to 93.8 mo). Demographic and treatment variables were similar except median prescribed margin dose was significantly lower in immunotherapy group (20 vs. 22 Gy, P<0.0001). Median overall survival (OS) was 27.2 months (immunotherapy) and 14.9 months (nonimmunotherapy), P=0.14. Furthermore, patients treated with immune checkpoint inhibitor (ICI) had even better median OS compared with those who never received ICI (33 vs. 16.7 mo, P=0.03). Factors associated with improved LC were use of ICI (P=0.002) and lesion size <1000 mm3 (P=0.046). There was no difference in incidence of radiation necrosis between the 2 groups (P=0.67). Patients with RCC BM undergoing SRS can experience prolonged survival when treated with ICI. Equally effective LC of BM was achieved when treated with immunotherapy using a 2 Gy decrease in SRS dose without increasing the risk of central nervous system toxicity.

The Effect of Allergen Immunotherapy on the Development of New Sensitization in Children.

Aim:The protective effect of allergen immunotherapy against a new allergic sensitization is controversial. This study aimed to investigate the effect of allergen immunotherapy on new allergic sensitization in children.Materials and Methods:The study included 50 patients who received immunotherapy for at least 3 years, and whose skin prick tests were repeated at intervals of at least 3 years (31 patients for house dust mite immunotherapy, 19 patients for pollen immunotherapy), and 69 controls with similar characteristics.Results:The number of patients who developed a new sensitization was similar both in the groups of patients who received house dust mite and pollen immunotherapy, and the control group. There was no significant difference between the first and last skin prick tests of the patients who received house dust mite and pollen immunotherapy; however, in the control groups, a significant increase in sensitivity to tree pollens (n = 2, 5.4%; n = 8, 21.6%) and weed pollens (n = 7, 26.9%; n = 14, 53.8%) was detected (P = .031 and P = .039). While allergen sensitivities in the first tests of the pollen immunotherapy group and the control group were similar, weed pollen sensitivity was significantly higher in the last tests of the control group (n = 14, 53.8%; n = 4, 21.1%, P = .027). It was determined that the presence of weed pollen sensitization (OR: 8.1, 95% CI: 1.5-42.4) and having asthma (OR: 3.5, 95% CI: 1.3-10.8) increases the risk of new sensitization in all groups.Conclusion:Allergen immunotherapy has been found to protect against new sensitization to tree and weed pollens. However, this effect was insignificant in the multivariate analysis. Weed pollen sensitization and the presence of asthma are related to the development of new sensitization.

Different prognostic implications of hepatic metastasis according to front-line treatment in non-small cell lung cancer: a real-world retrospective study.

BackgroundAlthough liver metastasis occurs in approximately 15% of metastatic non-small cell lung cancer (NSCLC) patients with poor prognosis, its prognostic effect in patients who receive immunotherapy is unclear. This study aimed to verify the effects of liver metastasis on the prognosis of metastatic NSCLC patients according to their first-line treatment.MethodsPatients who were initially diagnosed with stage 4 NSCLC from January 2015 to December 2019 were analyzed in this retrospective real-world data-based study. The patients were divided into three groups according to the type of first-line chemotherapy they received: cytotoxic, targeted, and immunotherapy. Prognosis was then compared depending on the presence of liver metastasis in each treatment group.ResultsAmong the 1,470 patients, 723 (49.2%) received cytotoxic chemotherapy, 678 (46.1%) received targeted therapy, and 69 (4.7%) received immunotherapy as their first-line chemotherapy. A total of 234 (15.9%) patients had liver metastasis at the initial diagnosis. The mean patient age was 63.7 years, and 59.1% were male. There was no difference in overall survival (OS) in the immunotherapy group in patients with or without liver metastasis (11.7 vs. 13.0 months, P=0.968); however, patients with liver metastasis had worse outcomes in the cytotoxic and targeted therapy groups compared to patients without liver metastasis. Furthermore, in patients with liver metastasis, the immunotherapy group had a longer OS than the cytotoxic chemotherapy group (11.7 vs. 4.4 months, P<0.001). Liver metastasis was associated with poor outcomes (hazard ratio of 1.438), as were age, male sex, bone, adrenal gland, or soft tissue metastasis, and three or more metastatic sites; however, lymph node, brain, collateral lung, and pleura metastasis did not affect prognosis.ConclusionsAlthough liver metastasis was associated with poor outcomes, it did not affect prognosis in patients who received immunotherapy.

Platform study of genotyping-guided precision medicine for rare solid tumours: a study protocol for a phase II, non-randomised, 18-month, open-label, multiarm, single-centre clinical trial testing the safety and efficacy of multiple Chinese-approved targeted drugs and PD-1 inhibitors in the treatment of metastatic rare tumours

IntroductionLimited clinical studies have been conducted on rare solid tumours, and there are few guidelines on the diagnosis and treatment, including experiences with targeted therapy and immunotherapy, of rare solid...

MO153RENAL FUNCTIONS OUTCOME IN METASTATIC NON SMALL LUNG CARCINOMA PATIENTS: THE RISK OF AKI IN FIRST LINE THERAPY

Abstract Background and Aims The optimal use of immune and target therapies, the optimal use of standard chemotherapy (CT) is of paramount importance, especially for patients affected by chronic kidney disease (CKD) who require dose adjustment according to the glomerular filtration rate (GFR) to avoid acute kidney injury (AKI) establishment. Immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy (CT) are options for the palliative treatment of metastatic non-small cell lung cancer (NSCLC). Recently, CT in combination with immune-checkpoint inhibitors has become the treatment of choice for this setting of patients. Therefore, it is fundamental to investigate the potential nephrotoxic effects of both treatments and their potential additive effects on renal function. Aim of our study was to compare the nephrotoxic effect of both ICIs and CT (cisplatin and carboplatin-based) in a consecutive cohort of patients affected by metastatic NSCLC. Method A consecutive cohort of 126 patients treated in first-line for NSLCL was enrolled in a single tertiary Hospital between 2018 and 2020. Inclusion criteria were: age (&amp;gt; 18 years old), eGFR (&amp;gt; 15 ml/min/1.73), histological diagnosis of metastatic NSCLC. Each patient underwent immunotherapy or CT according to clinical conditions, comorbidities and programmed death ligand 1 (PD-L1) expression status. eGFR (using CKD-EPI formula 2009) was detected at baseline and after each cycle of immunotherapy or CT (using cisplatin or carboplatin) in order to determine the correct renal status using the K-DIGO 2012 guidelines for AKI stages and CKD classes. Pts were subdivided into CKD categories G according to their eGFR values before and after the treatment. AKI onset was evaluated by rise in creatine levels according to K-DIGO criteria. Clinical stage according to cTNM (AJCC TNM system-2019) was collected at baseline before the first treatment. Comorbidities (e.g., diabetes, blood hypertension, overweight and obesity) were also included. Comparison between numerical variables was performed using linear regressions; between groups using Kruskal-Wallis rank sum test for numerical variables and Pearson’s Chi square test for categorical variables. Log rank test was used to test differences between groups in terms of AKI onset during the therapy. Results Clinical and pathological characteristics are reported in table 1. From the analysis, no significative differences were detected between Immunotherapy and CT group for age, gender, basal serum creatinine, basal eGFR, basal BMI, diagnosis of diabetes, hypertension, basal CKD G group or overall AKI onset. Treatment cycles were significantly different between the two groups (p&amp;lt;0.001) with a short median number of cycles for the CT group. No significative difference in terms of decay of eGFR calculated as final-basal values was detected (p=0.8). AKI onset over cycles was significantly different between the two groups (p=0.02), observing a higher risk of developing earlier AKI for CT group (cisplatin or carboplatin) (13,9%) with respect to immunotherapy (7,4%) (figure 1 and 2). Conclusion Our study highlights that both cisplatin and carboplatin-based CT displays an augmented incidence of AKI development after a lower number of therapy cycles in respect of immunotherapy. The nephrotoxic effects of combined therapy for NSLCL should be always evaluated by nephrologist during the treatment of NSLCL patients to avoid an augmented risk of AKI derived from the combination of immunotherapy and CT in first line.

Real-World Survival Outcomes Associated With First-Line Immunotherapy, Targeted Therapy, and Combination Therapy for Metastatic Clear Cell Renal Cell Carcinoma

Clinical trials have shown an overall survival (OS) benefit associated with first-line immunotherapy (IT) and combination targeted therapy (TT) and IT regimens compared with TT among patients with metastatic clear cell renal cell carcinoma (RCC). Generalizability of these findings in a real-world cohort outside of a clinical trial setting is unclear. To assess the association of first-line TT, IT, and combination TT and IT regimens with OS in a real-world cohort of patients with metastatic clear cell RCC. This retrospective propensity-matched cohort study identified 5872 patients with metastatic clear cell RCC in the National Cancer Database from January 1, 2015, to December 31, 2017, who received first-line TT, IT, or combination TT and IT and were not treated on a clinical trial protocol. Patients were stratified by first-line systemic treatment. Statistical analysis was conducted from October 1 to December 1, 2020. The primary outcome was OS from the date of diagnosis to death or censoring at last follow-up. After 1:1:1 nearest-neighbor caliper matching of propensity scores, survival analyses were conducted using Cox proportional hazards regression and Kaplan-Meier estimates. The final study population included 5872 patients (TT group: n = 4755 [81%]; 3332 men [70%]; median age, 64 years [interquartile range, 57-71 years]; IT group: n = 638 [11%]; 475 men [74%]; median age, 61 years [interquartile range, 54-69 years]; and combination TT and IT group: n = 479 [8%]; 321 men [67%]; median age, 62 years [interquartile range, 55-69 years]), and the matched cohort included 1437 patients (479 per treatment group). Patients in the IT and combination TT and IT groups were younger than those in the TT group, had fewer comorbid conditions (Charlson-Deyo score of 0, 480 of 638 [75%] in the TT group, 356 of 479 [74%] in the IT group, and 3273 of 4755 [69%] in the combination TT and IT group), and were more often treated at academic centers (315 of 638 [49%], 216 of 479 [45%], and 1935 of 4755 [41%], respectively). Both first-line IT and combination TT and IT were associated with improved OS compared with first-line TT for patients with metastatic clear cell RCC (IT group: hazard ratio [HR], 0.60 [95% CI, 0.48-0.75]; P < .001; combination TT and IT group: HR, 0.74 [95% CI, 0.60-0.91]; P = .005). No survival difference was seen between the IT and combination TT and IT groups (combination TT and IT: HR, 1.24 [95% CI, 0.98-1.56]; P = .08). This study suggests that both first-line IT and combination TT and IT were associated with improved OS compared with first-line TT for patients with metastatic clear cell RCC. These findings are similar to those identified in recently reported clinical trials, lending confidence to the broader applicability of these findings outside of a clinical trial setting.

Real-world outcomes for patients with metastatic non-small cell lung cancer according to first-line treatment

Metastatic non-small cell lung cancer is a disease with a poor prognosis and things may improve with the rise of immunotherapy. Clinical trials proved that immunotherapy had better results on survival than chemotherapy as first-line treatment for patients with metastatic lung cancer (MLC). Although clinical trials have strong internal validity, they suffer from restrictive selection criterions and it can be difficult to generalize to real-life patients. We aimed to evaluate if the results of survival when comparing immunotherapy with chemotherapy as first-line therapy for MLC in real-life data are similar to those from clinical trials. All consecutive patients included in the retrospective Epidemio-Strategy Medico Economic (ESME-AMLC– NCT03848052 ) program with a non-small cell MLC treated with a systemic treatment (either chemotherapy alone or immunotherapy alone) between January 2015 and December 2018. Patients diagnosed with a tumor with EGFR, KRAS, ROS or BRAF mutation were excluded. Confounding and indication biases were taken account by analyzing causal relation between treatment allocation and survival by constructing a directed acyclic graph. Progression-free survival was analyzed as secondary outcome. ESME database included 21,169 patients and 5,255 individuals were included in the study: 5055 treated with chemotherapy, 200 treated with immunotherapy. Median age at diagnosis was 63 years and male represented 67.7% of the population. Median OS in immunotherapy group was 16.4 months (95% CI = [14.1–NR]) and was higher than in chemotherapy group (11.6 months; 95% CI = [11.0–12.2]). In Cox models analyzes, immunotherapy group had better results after 3 months for subjects with performance status (PS) 0–1 (HR = 0.59; 95% CI = [0.42–0.83], P = 0.003) but had poor results before 3 months for subjects with 2, 3 or 4 PS (HR = 2.28; 95% CI = [1.17–4.47], P = 0.016). Our results were in favor of benefits on survival of the immunotherapy as first-line treatment for MLC after 3 months for patients in good health condition, as found in clinical trials.

Effect of immunotherapy on survival outcomes in prostate cancer: Systematic review and meta-analysis.

e17030 Background: Prostate cancer is one of the leading cancers in men with an estimated 191,930 new cases in 2020 in the USA alone. Treatment options for metastatic castration resistant prostate cancer (mCRPC) have evolved in recent years. Immunotherapy involving vaccines like sipuleucel-T, PROSTVAC and immune checkpoint inhibitors have been evaluated in these patients. We present a systematic review and meta-analysis of the randomized controlled trials (RCTs) testing the effect of immunotherapy in mCRPC. Methods: A systematic search was performed using PubMed, Embase and the Cochrane library without language limitations from inception to January 3, 2021. The primary outcome was overall survival (OS) and secondary outcomes were progression free survival (PFS), prostate specific antigen (PSA) reduction ≥ 50% and incidence of grade 3-4 adverse events. The analysis of OS, PFS was done using random effects hazard ratio (HR) by generic inverse variance method and analysis of PSA reduction ≥ 50% and grade 3-4 adverse events was done using random effects risk ratio (RR) by the Mantel-Haenszel method. Results: 12 RCTs comprising 4109 patients were included in the analysis. There was a statistically significant improvement in OS (HR 0.89; 95% CI (0.81, 0.97)) and PFS (HR 0.83; 95% CI (0.76, 0.92)) in the immunotherapy arm compared to placebo or standard treatment arms with moderate quality of evidence. Patients in the immunotherapy group had significant reduction in PSA ≥ 50% (RR 1.71; 95% CI (1.09, 2.68)) but also had statistically significant increased risk of grade 3-4 adverse events (RR (1.25; 95% CI (1.02, 1.54)) when compared to placebo and the standard treatment group. Subgroup analysis showed that the use of vaccine therapy in prostate cancer leads to significant improvement in OS (HR 0.83; 95% CI (0.74, 0.93)) and PFS (HR 0.80; 95% CI (0.67, 0.95)) compared to placebo and standard treatment. The use of immune checkpoint inhibitors was not associated with statistically significant improvement in OS (HR 0.98; 95% CI (0.88, 1.09)) but is associated with improvement in PFS (HR 0.87; 95%CI (0.81, 0.94)). Conclusions: This meta-analysis showed that immunotherapy led to significant improvement in OS, PFS and PSA reduction of ≥ 50%. However, there is an increased incidence of grade 3-4 adverse events with the use of immunotherapy when compared to other standard therapies and placebo. The improvement in overall survival is limited to the use of vaccine therapy and not to immune checkpoint inhibitors. Careful use of selective forms of immunotherapy in mCRPC can lead to greater improvement in survival.

Metastatic site-specific utilization and outcome of immunotherapy in stage IV melanoma: A national perspective.

e21525 Background: Metastatic melanoma is an aggressive disease with a rapid systemic dissemination. We evaluated the effect of metastatic sites on the utilization immunotherapy and survival outcomes in stage IV melanoma. Methods: The National Cancer Database from 2010-2017 was queried for stage IV melanoma. Those with missing relevant data were excluded. Patients were grouped into five categories based on metastatic sites: lung metastasis only, brain metastasis only, liver metastasis only, bone metastasis only and multiple sites metastasis. Multivariable logistic regression was used to predict use of immunotherapy. Effects of immunotherapy on overall survival were assessed using Kaplan-Meier curves and Cox proportional hazards model. Results: A total 12, 315 were included in the study, among whom 2206 (17.9%) had lung metastasis only, 1,873 (15.2%) had brain metastasis only, 785 (6.4%) had liver metastasis only, 662 (5.4%) had bone metastasis only and 5,983 (48.6%) presented with multiple metastatic sites. Surgery at primary site was performed in 34.3% of patients with bone metastasis (p&lt;0.001), and radiation therapy was delivered to 69.2% patients with brain metastasis (p&lt;0.001). Site of metastatic disease was associated with immunotherapy utilization, with multiple sites (OR = 1.149, p=0.012), and distant lymph nodes (OR=2.867, p&lt;0.001) demonstrating the strongest association, while patients with oligo brain metastasis were less likely to receive immunotherapy (OR = 0.486, p&lt;0.001). Immunotherapy is associated with superior survival among metastatic melanoma patients (HR=0.433, P&lt;0.001). The Kaplan-Meier curves showed the median overall survival among the immunotherapy group was 33.7 months for lung metastasis (vs. 13.4 months without immunotherapy, HR=0.633, p&lt;0.001), 25 months for brain metastasis (vs. 6.7 months without immunotherapy, HR=0.447, P&lt;0.001), 16.8 months for liver metastasis (vs. 4.2 months without immunotherapy, HR=0.449, P&lt;0.001), 18.3 months in bone metastasis (vs. 7.6 months without immunotherapy, HR=0.615, p&lt;0.001) and 12.1 months in multiple metastasis (vs. 3.8 months without immunotherapy, HR=0.338, p&lt;0.001). Conclusions: Utilization of immunotherapy is influenced by location of metastatic disease in stage IV melanoma. Overall survival is improved for patients treated with immunotherapy.[Table: see text]

Albumin-bound paclitaxel plus PD-1/PD-L1 inhibitor versus second-line chemotherapy for patients with recurrent small cell lung cancer.

e20591 Background: The main aim of this study was to evaluate the efficiency of albumin-bound paclitaxel (nab-PTX) plus PD-1/PD-L1 inhibitor versus second-line chemotherapy in small cell lung cancer (SCLC) patients who have failure to the first-line standard treatment. Methods: We retrospectively collected patients’ data from medical records between January 2015 to July 2020 in Shandong Cancer Hospital and Institute. Consecutive 42 patients who were treated with nab-PTX plus PD-1/PD-L1 inhibitor were enrolled and compared with, 126 patients who received second-line chemotherapy (1:3 matched with patient and tumor characteristics). Progress free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) were evaluated for each group. Results: Patients treated with nab-PTX plus immunotherapy group and second-line chemotherapy group achieved the median PFS of 5.6 months and 3.3 months ( p = 0.043), respectively. The median OS were 7.7 months and 6.3 months ( p = 0.021), respectively. The ORR and DCR were also higher in nab-PTX plus PD-1/PD-L1 inhibitor group (ORR: 33.3% vs 20.6%, p = 0.094; DCR: 61.9% vs 41.3%, p = 0.020, respectively). The most common incidences of grade ≥3 adverse events were leukopenia and neutropenia, there were no significance difference between the two groups. Conclusions: Albumin-bound paclitaxel plus PD-1/PD-L1 inhibitor conferred higher ORR and DCR, and improved PFS and OS in SCLC patients failed with first-line treatment. Further prospective and randomized trial that directly compares the treatments is urgently warranted.

Treatment outcomes in renal cell carcinoma patients with metastases to the pancreas and other sites.

4557 Background: Metastatic RCC (mRCC) involving the pancreas is distinct from RCC involving other metastatic sites and is characterized by an indolent clinical course, heightened angiogenesis, and an inflamed stroma (PMID: 32271170). We previously reported on outcomes of RCC patients (pts) with pancreatic oligometastasis (ASCO GU 2020). We now report on outcomes in pts with mRCC involving the pancreas in conjunction with other metastases (mets). Methods: We conducted a retrospective, multi-institutional study of mRCC pts with mets to the pancreas and other sites. Data on pt demographics, tumor characteristics, systemic therapy, and outcomes were collected. Pts were classified based on treatment category: immunotherapy (IO) or vascular endothelial growth factor/receptor inhibitors (VEGFI). Outcomes measured included objective response rates (ORR), time-on-treatment (TOT), and overall survival (OS). Results: The analysis included 229 pts from 9 institutions, diagnosed between 1985-2020. Of these, 211 (92%) had clear-cell histology; 131 (57%) had nephrectomy; 41 (18%) had local pancreas-directed therapy; 111 (48%) had synchronous presentation of disease in the pancreas and other sites at time of mets. IMDC risk was favorable in 33%, intermediate in 41%, poor in 11%, and unknown in 15% pts. Median lines of therapy was 2 (range 0-9). Of 219 pts who received first-line (1L) therapy, 151 (69%) had VEGFI therapy, 41 (19%) had IO, and 18 (8%) had VEGFI/IO combination (Table). The IO group included 21 pts on checkpoint inhibitor (CPI), 16 pts on HD-IL2, 4 pts on other IO. 1L ORR was 39.7% for VEGFI (95% CI 31.8-48.0) and 31.7% for IO (95% CI 18.1-48.1) and was not statistically significant (NS, OR 1.4, 95% CI 0.65-3.23, p = 0.371). Median TOT for 1L therapy was 11.6m for VEGFI and 6.5m for IO (p = 0.0106). With a median follow-up of 51.5m, the median OS (mOS) for all pts from time of metastatic disease was 7.7 years (y) (95% CI 6.3-10.3). The mOS for pts who received 1L VEGFI was 7.6y (95% CI 5.5-9.5) and was not reached (NR) for those who got 1L IO (95%CI 6.5-NR); this difference was significant with an unadjusted p-value of 0.029. The pair-wise comparison between mOS of the 1L CPI subgroup compared to that of the 1L VEGFI group was significant (p = 0.0148). Conclusions: Consistent with the literature, mRCC pts with involvement of the pancreas in this study have prolonged OS compared to historical OS for the standard mRCC population. Additionally, our findings suggest that the choice of first-line therapy may impact outcomes. Additional analyses will be presented.[Table: see text]

Abstract No. 211 Early hepatic arterial embolization or concomitant immunotherapy are associated with improved overall survival in patients with metastatic adrenocortical carcinoma

To evaluate factors associated with overall survival and local tumor progression-free survival after hepatic arterial embolization (HAE) of metastatic adrenocortical carcinoma (ACC). This is a retrospective Institutional Review Board approved single-institution study with 16 patients (9 women, 7 men; median age, 46 years; range 19-73) with ACC that underwent HAE between 2010 and 2019. Patients were divided into three groups: systemic therapy-naïve (n = 5), chemotherapy-refractory (n = 6), and immunotherapy (n = 5). Variables including treatment history, functional status of tumor, tumor histology, tumor burden, procedure details, and complications were also analyzed. Overall survival (OS) and local tumor progression-free survival (LPFS) were estimated using the Kaplan-Meier method and hazard ratios were estimated using Cox proportional hazards model. Radiographic responses (complete response [CR], partial response [PR], stable disease [SD], and progressive disease [PD]) at 3 months were evaluated by mRECIST criteria. Median OS was 27.7 months (95% Confidence Interval [CI] = 0-56 months). Systemic therapy-naïve group (hazard ratio [HR] = 0.15, CI = 0.02-0.9) and immunotherapy group ([HR] = 0.09, CI = 0.01-0.7) had prolonged OS compared with the chemotherapy-refractory group (P = 0.01). Median LPFS from time of HAE was 10 months (95% confidence interval [CI] = 2.4-17 months).Tumor burden < 25% was associated with significantly longer LPFS (P = 0.008). Objective response (OR) was observed in 9/16 patients (56%) (CR in 5/16 (31%) and PR in 4/16 (25%) patients), while 5/16 (31%) had SD and 2/16 (13%) had PD. 7/16 (44%) patients had hormone-secreting tumors (3/5 in systemic-naïve group, 2/5 in immunotherapy group, and 2/6 in chemo-refractory group). This study demonstrates an association between early HAE or concomitant immunotherapy and improved OS in patients with metastatic ACC. Low tumor burden is associated with longer LPFS.

Cytokine-induced killer cells/dendritic cells and cytokine-induced killer cells immunotherapy for the treatment of esophageal cancer: A meta-analysis.

Objectives:This meta-analysis was designed to systematically evaluate whether autologous cytokine-induced killer cells (CIK) or dendritic cells and cytokine-induced killer cells (DC-CIK) immunotherapy combined with chemotherapy can improve the therapeutic effect and safety of chemotherapy in esophageal cancer (EC).Materials and methods:Randomized controlled trials (RCTs) were electronically searched databases including CNKI, WanFang, WeiPu, CBMDisc, PubMed, Web of Science, EMbase, the Cochrane Library, and Clinical Trials. The databases were searched for articles published until June 2019. Two researchers independently screened the literature, extracted data, and evaluated the quality of the included literature. Meta-analysis was performed using RevMan5.3.Results:Seventeen studies (1416 participants) were included. The differences between CIK/DC-CIK combination chemotherapy and chemotherapy alone were significant. The results displayed that the number of CD3+, CD4+, CD4+/CD8+, and NK cells was significantly increased after 1 to 2 weeks of treatment with CIK/DC-CIK cells in the treatment group (all P < .05). In addition, the results shown that 1-year overall survival was significantly prolonged (P < .0001) and quality of life was improved (P = .001) in EC chemotherapy combined with immunotherapy groups compared with conventional treatment. Furthermore, cytokine expression levels of interleukin 2 (IL-2), tumor necrosis factor α (TNF-α), and interleukin 12 (IL-12) were significantly increased (P = .0003) as well as the levels of immunoglobulins were elevated (P < .00001). Serum levels of tumor marker molecules, carcinoembryonic antigen (CEA), carbohydrate antigen (CA)-199, and CA-125 were lower in treatment groups than that of control groups (P < .00001). No fatal adverse reactions were noted (P = .04).Conclusions:It is safe and effective for patients to use chemotherapy combined with CIK/DC-CIK immunotherapy. Immunotherapy can simultaneously improve the antitumor immune response. Specifically, DC-CIK cells can increase T lymphocyte subsets, CIK cells, NK cells, and immunoglobulins in peripheral blood to enhance antitumor immunity. Therefore, combination therapy enhances the immune function and improves the therapeutic efficacy of patients with EC.

Perioperative safety and feasibility outcomes of stage IIIA-N2 non-small cell lung cancer following neoadjuvant immunotherapy or neoadjuvant chemotherapy: a retrospective study.

BackgroundWe sought to determine the perioperative safety and feasibility outcomes of stage IIIA (N2) non-small cell lung cancer (NSCLC) following neoadjuvant immunotherapy or neoadjuvant chemotherapy.MethodsThe clinical details of patients who attended the Affiliated Hospital of Qingdao University between January 2019 and December 2020 were retrospectively evaluated. Eligible patients had pathologically proven stage IIIA (N2) NSCLC and were randomly prescribed neoadjuvant therapy. Those in the neoadjuvant immunotherapy group received two cycles of nivolumab (3 mg/kg) and those in the control group received neoadjuvant chemotherapy (1,000 mg/m2 gemcitabine and 80 mg/m2 cisplatin). All patients were scheduled to undergo surgery. The primary endpoint was the risk of major complications within 30 days of surgery and the secondary endpoints were interval to surgery and 30-day mortality.ResultsA total of 107 eligible patients were evaluated of whom 25 were allocated to the neoadjuvant immunotherapy group and 82 to the neoadjuvant chemotherapy group. The median interval to surgery was similar in the two groups at 29.2 days [95% confidence interval (CI), 27.1 to 31.4 days] in the immunotherapy group and 28.7 days (95% CI, 27.6 to 29.8 days) in the chemotherapy group (P=0.656). While treatment-related adverse events were reported in most patients, all 25 patients completed two cycles of neoadjuvant immunotherapy and 80 of 82 patients completed two cycles of neoadjuvant chemotherapy, although one patient in the latter group died within 30 days of surgery. There was no statistically significant difference between the groups in the probability of grade 3 or higher postoperative complications within 30 days after surgery (P=0.757).ConclusionsMost patients achieved the primary and secondary endpoints of the study. However, the major pathological response (MPR) showed statistically significant differences between the neoadjuvant immunotherapy and neoadjuvant chemotherapy groups.